Carfilzomib-induced acute cardiotoxicity is mediated through angiotensin and caused by cardiomyocyte energy depletion

Author(s):
Mendez, M.; Andrej, B.; Florea, B.I. (0000-0001-7114-2266); Christian, Z.; Overkleeft, H.S. (0000-0001-6992-4760); Lenka, B.; Driessen, C.
Published
2021
Publication type
Abstract

Abstract

Carfi lzomib (CFZ) treatment increases the survival of patients with relapsed/refractory MM, but it is associated with a higher incidence of cardiovascular adverse events not commonly observed after bortezomib (BTZ). Both CFZ and BTZ inhibit the rate-limiting proteasome beta 5 subunit activity at lower concentrations. However, only CFZ co-inhibits the activity of proteasome beta 5 and beta 2 subunits at higher doses, in contrast to the beta 5 and beta 1 co-inhibition provided by high dose BTZ. We hypothesized that the unique beta 5 and beta 2 subunit inhibition pattern explains the CFZ-related acute cardiotoxicity.

Date issued
2021-10-01
Language
English
Publisher
CIG MEDIA GROUP, LP
Is part of
Clinical Lymphoma, Myeloma and Leukemia (2021), Vol. 21, no. 2, p. S122
hdl
1887/3249372
doi
10.1016/S2152-2650(21)02285-0
URL
https://www.sciencedirect.com/science/article/pii/S2152265021022850?casa_token=qPHdLYyJBaIAAAAA:aBbclQjsy48RpeeKuiGlIIAcmMDj9oKLABLt9GHxIhTmWlLt-fwibaC3apq4B5n_-v1NlhDt